Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women (NCT00608062), a randomized na study. The primary outcome is Arterial Stiffness (Carotid Artery Compliance) During Saline.

2. Clinical Question

In statistical terms, the question concerns a continuous vascular measure observed at multiple specified times, across groups defined by menopausal status and assigned patch treatment. The registry record describes the study’s biological motivation as investigating why arteries stiffen as women go through menopause, including the possible roles of oxidative stress and the arteries’ ability to dilate. Those statements describe the motivation, not findings. The record does not establish that the trial tested every proposed mechanism, nor does it report results for oxidative stress or dilation as separate outcomes.

The primary-outcome description combines early and late perimenopausal participants into one group. The arm descriptions retain separate early and late perimenopausal assignments, so the outcome population description and the treatment-arm descriptions are not identical in level of detail. No further explanation of that distinction is reported in the registry record.

3. Trial Design

The registry record identifies this as a randomized, double-masked, parallel study. Enrollment was 155. Its phase is listed as NA, and its status is completed. The study is titled Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women; its official title is Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency. The sponsor is the University of Colorado, Denver.

The described interventions were ganirelix acetate, a transdermal estradiol patch and a transdermal placebo patch. The arm descriptions pair GnRHant with estradiol or placebo within premenopausal, early perimenopausal, late perimenopausal and postmenopausal groups. The registry record does not report additional detail about the sequence of treatment assignment, the masking procedures, or whether treatment implementation differed across these groups.

The listed primary outcome is arterial stiffness measured as carotid artery compliance. Measurement is described at baseline, day 4 of GnRHant, and day 7 of GnRHant with estradiol or placebo treatment. For the primary outcome, early and late perimenopausal participants were collapsed into one perimenopausal group. The record does not describe the statistical model used to handle repeated measurements or group structure.

The study start is listed as 2007-03, and primary completion as 2012-10-25. The record lists arterial stiffening, aging and menopause as conditions. It does not report a protocol rationale for enrollment, the method used to determine the planned enrollment, or details of allocation concealment. The enrollment figure describes the overall study; arm-specific enrollment for the primary endpoint is not reported in the registry record.

Randomization and masking are design features, not evidence by themselves that groups were balanced or that bias was absent. Assessing those questions would require information about baseline characteristics, adherence, withdrawals, masking success and the analysis procedures. Those details are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 155 women consented to participate. During screening, 33 women did not qualify (12 premenopausal, 14 perimenopausal \[11 early- and 3 late\], and 7 postmenopausal). Twenty-three withdrew from participation before baseline testing and 7 women withdrew from participation after baseline testing but prior to randomization.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Early and late perimenopausal were collapsed into 1 perimenopausal group

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: For primary outcome brachial artery FMD, 91 completed the study. Four participants did not have usable FMD data due to poor ultrasound image quality or technical issues with image acquisition; baseline analysis and results for the remaining 87 women are presented.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Arterial Stiffness (Carotid Artery Compliance) During Saline, measured over Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment.

The primary endpoint is carotid artery compliance during saline, reported as a mean with standard deviation. It is measured using carotid artery ultrasound and brachial artery blood pressure. The stated unit is mm2/mm Hg×10-1. The registry record specifies measurements at baseline, day 4 of GnRHant, and day 7 of GnRHant with estradiol or placebo treatment.

Compliance is a continuous measure of how readily an artery expands in response to pressure. As a general statistical interpretation, a continuous measurement can describe the magnitude of a physiological characteristic rather than classifying participants only into categories. The endpoint is relevant to the study’s stated focus because the study description concerns arterial stiffening and the ability of arteries to expand or dilate. That relevance does not establish that the endpoint captures every aspect of arterial stiffness or every proposed biological mechanism.

The reported mean describes the group’s average measurement; the standard deviation describes variation among measurements. These summaries are not themselves a treatment effect. To evaluate a treatment contrast, readers would need the group estimates and a comparison between them, with an uncertainty measure and a clear account of the analysis. Numerical estimates for this primary endpoint, including the treatment comparisons, are not reported in the registry record.

There are multiple specified measurement times. Changes over time and differences between treatment assignments are distinct statistical questions, and the registry record does not report which contrast or time point was designated for a single numerical treatment-effect estimate. It also does not report how measurements from the same participant were handled statistically.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a randomized, double-masked, parallel design. In general, randomization assigns participants to treatment groups by chance, which can reduce systematic differences between groups at the start of a study. Masking is intended to limit the influence of treatment knowledge on participants or study personnel, depending on who is masked. The record identifies the study as double-masked but does not specify which parties were masked or how masking was maintained. These design labels do not replace an assessment of how the study was conducted.

What does a mean with standard deviation describe?

The primary endpoint is continuous and is summarized in the registry as a mean with standard deviation. In general, the mean is the arithmetic average of measurements in a group. The standard deviation describes how dispersed individual measurements are around that average. It is not the same as the standard error, which describes the sampling uncertainty of an estimated mean, and it is not a confidence interval for a treatment difference. The registry record does not report the endpoint means or standard deviations, so these summaries cannot be interpreted numerically for this study.

A comparison of group means is different from simply observing that one group’s mean is higher or lower. Statistical inference for a difference depends on the variability and number of observations, as well as the analysis method and design. A confidence interval, in general, gives a range of effect estimates compatible with the data and the assumptions of the analysis at a stated confidence level. It communicates precision as well as direction and magnitude. No primary-endpoint confidence interval is reported in the registry record.

Why do the measurement times matter?

The endpoint description specifies baseline, day 4 of GnRHant, and day 7 of GnRHant with estradiol or placebo treatment. These are repeated measurements over time, rather than one measurement per participant. In general, measurements from the same participant tend to be related, so analyses should account for that within-participant dependence. A method that treats all repeated measurements as if they came from unrelated participants may give inappropriate uncertainty estimates. The record does not identify the method used, the contrast of interest, or how baseline measurements were incorporated.

Different statistical questions can be asked of repeated measurements. A comparison at a particular time asks about groups at that time. A comparison of change asks how measurements shift from baseline. A model of the full pattern over time asks whether changes differ across assigned groups. These approaches need not estimate the same quantity. The registry record lists the measurement schedule but does not report which estimand or model was used for the primary analysis.

How should the group structure be understood?

The arm descriptions distinguish premenopausal, early perimenopausal, late perimenopausal and postmenopausal groups, each paired with GnRHant plus estradiol or GnRHant plus placebo. The primary outcome description says early and late perimenopausal participants were collapsed into one perimenopausal group. This is important because an analysis using a combined group answers a different question from one estimating separate effects for early and late perimenopausal groups. The record does not explain the analysis rationale or provide separate outcome estimates.

In general, subgroup comparisons can be less precise than an overall comparison when they use fewer observations. A subgroup pattern should not automatically be treated as evidence that treatment effects truly differ between groups; that conclusion depends on a suitable interaction analysis and its uncertainty. The registry record does not report such analyses or their results.

What can be inferred from the planning description?

The registry record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such an illustration is not the trial’s design justification and does not establish the study’s actual power. Planning calculations depend on assumptions about the target effect, variability, allocation and analysis. The registry record does not report the trial’s own sample-size justification, and numerical planning results are not available in the registry record described for this explanation.

In general, observed power calculated after a study is not a substitute for an effect estimate and its confidence interval. The observed data and their precision are more directly useful for interpreting what a study found. No primary endpoint estimate is reported in the registry record, so neither an observed effect nor its precision can be assessed.

What is not reported about the analysis?

The record does not report the primary analysis model, its assumptions, the treatment contrast used, the handling of repeated observations, or whether adjustments were made for baseline values or other variables. It does not report confidence intervals or primary-outcome p-values. Those omissions limit reproducibility and prevent readers from checking whether the statistical analysis matched the randomized design and repeated-measure structure. General statistical principles explain why these details matter, but they do not reveal which method was used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint has multiple listed measurement times, and the registry record identifies eight outcome measures and three analyses. It also notes that the primary outcome has several categories or time points and was not reduced to one comparison. This makes the target of a single primary treatment-effect statement unclear from the record. Considering several outcomes, time points, groups or contrasts can create multiplicity: in general, the more inferential questions examined, the greater the chance of at least one apparently notable result arising by chance if no adjustment or prespecified hierarchy is used.

The registry record does not report a multiplicity strategy, a hierarchy of outcomes or contrasts, or which results were designated confirmatory. It also does not say whether any adjustment was made for multiple testing. Without that information, readers cannot determine how to interpret the statistical significance of any individual comparison; in this case, numerical primary-outcome tests are not reported in the record.

Missing-data handling and analysis populations are also not reported. The overall enrollment does not reveal how many participants had usable measurements at each time point or how many were included in each analysis. The record does not describe withdrawals, missing observations, exclusions after randomization, or any imputation or sensitivity analyses. In general, missingness can affect estimates if the participants with observed outcomes differ systematically from those without observed outcomes. The extent and consequences depend on the reasons for missingness and the analysis assumptions, neither of which can be assessed from this record.

The registry record also does not specify whether the primary analysis followed all randomized participants, used another population definition, or handled protocol deviations in a particular way. These details are needed to understand how the randomized assignment relates to the analyzed comparison. No conclusion about the magnitude or direction of bias from missing data or multiplicity is justified without further information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists serious and other adverse-event counts for six named groups. In the premenopausal GnRHant-plus-estradiol group, 12 participants were at risk, with 0 serious events, 8 other events and 0 deaths. In the premenopausal GnRHant-plus-placebo group, 12 were at risk, with 0 serious events, 4 other events and 0 deaths.

For early perimenopausal GnRHant plus estradiol, 19 participants were at risk, with 0 serious events, 9 other events and 0 deaths. For early perimenopausal GnRHant plus placebo, 21 were at risk, with 0 serious events, 8 other events and 0 deaths. In the postmenopausal GnRHant-plus-estradiol group, 13 were at risk, with 0 serious events, 5 other events and 0 deaths. In the postmenopausal GnRHant-plus-placebo group, 15 were at risk, with 0 serious events, 4 other events and 0 deaths.

These are counts, not comparative risk estimates. The registry record lists no terms among its top serious adverse events. It does not provide event descriptions for the other events in these group counts, nor does it report the adverse-event collection period or a statistical comparison. The adverse-event group listings do not include every arm description, so these figures should be read only for the groups explicitly listed. The absence of reported serious events in these groups does not establish that no other harms occurred or that treatments are equivalent in safety.

12. What the Result Does, and Does Not, Mean

The record establishes that the study was randomized, double-masked and parallel, and that it evaluated carotid artery compliance in relation to GnRHant with estradiol or placebo across menopausal groups. It also describes a biological motivation involving arterial stiffening, estrogen loss, oxidative stress and dilation. These features explain the study’s question, but they do not establish an answer.

The record does not report the numerical primary-outcome findings. Therefore, it cannot show whether carotid compliance differed between assigned groups, whether measurements changed over the specified time points, or how large or precise any difference might have been. No conclusion that a treatment improved, worsened or had no effect on the endpoint follows from the design description alone. A lack of reported results is not equivalent to a result of no difference.

The biological explanation also requires caution. A measurement of carotid artery compliance is relevant to arterial behavior, but the record does not report findings for oxidative stress or the proposed pathway connecting estrogen loss to arterial changes. It is not possible to infer that a particular mechanism caused or prevented arterial stiffening from the stated rationale or intervention names.

The safety counts are limited to the groups and categories listed. They record zero serious adverse events in each of those groups, along with other-event counts and zero deaths. Without event descriptions, observation periods, complete group reporting and comparative analyses, these counts do not establish a complete safety profile or rule out uncommon events.

A fuller interpretation would require the primary endpoint estimates at the relevant time points, a clearly defined treatment contrast, uncertainty intervals, and information about participants included in each analysis. Details about missing observations, multiplicity, and the statistical model would also help readers judge robustness. Until those results and methods are available, the defensible conclusion is limited to what the registry record describes: the study question, intervention assignments, endpoint and design, rather than an estimate of treatment effect.

13. Why This Trial Matters Statistically

This study raises a statistically informative design problem: a continuous vascular endpoint is measured repeatedly, while treatment assignments are described across several menopausal groups. Interpreting such a design requires clarity about the target comparison, the role of baseline, the handling of measurements from the same participant and whether early and late perimenopausal groups are combined. The registry record specifies some of this structure but does not report the analysis details or numerical endpoint results.

The distinction between a study’s rationale and its statistical evidence is especially important. The stated interest in estrogen loss, oxidative stress and arterial dilation motivates the endpoint and interventions. It does not demonstrate that those mechanisms were measured, nor that a treatment changed arterial compliance. Statistical interpretation depends on the observed estimates and their uncertainty, not on biological plausibility alone.

Randomization and double masking are useful design features, but their value for interpretation depends on implementation and analysis. Readers need to know which participants contributed outcome data, how repeated measurements were modeled, and which contrasts were planned. The record does not report those details. This limits assessment of internal validity, precision and the possibility that selective emphasis among outcomes or time points influenced interpretation.

The record also illustrates why safety counts and efficacy estimates answer different questions. Serious-event counts are reported for several groups, but the primary endpoint results are not. Counts of adverse events cannot substitute for a treatment-effect estimate for carotid artery compliance, and zero serious events in listed groups is not evidence that all clinically relevant harms are absent.

Statistically, the most consequential feature is not a particular numerical finding, because none is reported for the primary endpoint. It is the gap between a detailed question and an incomplete account of the estimate, uncertainty and analysis. Reporting the outcome estimates and methods would allow readers to distinguish a precise result from an uncertain one and to understand which population and comparison the result represents.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation for interpretation is that numerical primary-outcome results are not reported in the registry record. The record names the endpoint, its unit, summary type and measurement schedule, but gives no group-level means, standard deviations, treatment contrasts or uncertainty estimates. This prevents assessment of magnitude, direction and precision.

The primary outcome is described across multiple measurement times, while the registry record says the outcome has several categories or time points and was not reduced to one comparison. It does not identify a single contrast for interpretation or report the model used for repeated observations. Early and late perimenopausal groups are listed separately in the arm descriptions but are collapsed into one perimenopausal group in the primary-outcome description. The record does not explain the implications of that grouping choice or give results by subgroup.

The record reports overall enrollment but does not give primary-outcome sample sizes by group or time point. It does not describe missing measurements, participant withdrawals, analysis-population definitions, exclusions or sensitivity analyses. These omissions make it difficult to determine how complete the outcome data were or how well the analyzed participants represent the randomized groups.

It lists multiple outcome measures and analyses but does not report a multiplicity plan or analysis hierarchy. The primary statistical model, its assumptions and the treatment contrast are also not reported. Details of the masking procedures, allocation concealment, adherence and baseline characteristics are absent from the record. These are limitations of what can be assessed from the registry record; they do not establish that the study itself lacked such procedures or analyses.

Safety reporting is also limited: event descriptions for the other adverse-event counts and the collection period are not reported, and the listed adverse-event groups do not cover every described arm. The available counts therefore offer only a partial view of safety reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sex Hormones and Atherosclerosis Prevention in Perimenopausal Women — NCT00608062.
• Registry record last updated 2020-12-24; status last verified 2020-12.
• Results first posted 2020-12-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00608062 is a completed randomized, double-masked, parallel study sponsored by the University of Colorado, Denver, with enrollment of 155. It describes ganirelix acetate with a transdermal estradiol or placebo patch across premenopausal, early and late perimenopausal, and postmenopausal groups. The primary endpoint is carotid artery compliance during saline, measured at baseline, day 4 of GnRHant, and day 7 of GnRHant with estradiol or placebo. Early and late perimenopausal participants were collapsed into one group for the primary endpoint.

The registry record reports no numerical primary-outcome estimates or analysis details sufficient to interpret a treatment contrast. It lists serious and other adverse-event counts for six groups, with zero serious events and zero deaths in each listed group. Missing-data procedures, analysis populations, multiplicity handling and the primary statistical model are not reported in the registry record.